The efficiency of immune response against different pathogens, either induced by vaccination or by contact with the pathogen itself, depends on a number of complex phenomena, such as, antigen presentation by professional presenter cells, specific lymphocyte activation, cell differentiation, antibody production, and other humoral factors mediating cell communication. The underlying complexity of the immune response mechanisms is a rationale for the heterogeneous efficiency in controlling different infections or vaccine-induced responses. It is feasible that those phenomena determining the induction of acquired immunity may be enhanced by potentiating the antigen presentation phenomenon, a critical phase for inducing an effective immune response. The use of adjuvants has been relevant especially to potentiate vaccines with poor protector capacity, like influenza vaccine for instance.
There is a number of immunopotentiators or adjuvants in the state of the art, like aluminum hydroxide or phosphate. This adjuvant was first reported in 1926, and was the first authorized for human use. However, it bears some limitations, especially by inducing a strong T cell-mediated immune response [Chang S. et al. 2009], which is counter-producing instead of favorable in certain treatments. Additionally, aluminum hydroxide specifically exacerbates a cellular response, which is not adequate to prevent certain diseases where protection is particularly associated to the humoral immune response.
Another adjuvant used in human vaccines is described on EP0399843B1, a water-in-oil emulsion with squalene, known as MF59, which is used in combination with influenza vaccine. While this adjuvant has increased the humoral immune response when parenterally co-administered with the vaccine, the immunoenhancing effect of MF59 is limited in high-risk age groups, and the vaccine exhibits a poor efficiency in those groups. Another limitation of MF59 adjuvant is that its effectiveness has been demonstrated only when administered parenterally. MF59 has not shown any potentiating effect in the vaccine response when intranasally or orally administered [Boyce T G et al. 2000].
MF59 only potentiates the production of IgG-class antibodies, and when co-administered with influenza vaccine to the higher-risk groups it fails to induce a protection as efficient as the one it elicits when administered to younger individuals. Additionally, MF59 enhancer effect is limited to the parenteral route of administration for the vaccine.
In the state of the art, patent MX270782 describes GK-1 peptide as SEQ ID No. 1, an 18-amino acid sequence G-Y-Y-Y-P-S-D-P-N-T-F-Y-A-P-P-Y-S-A derived from a Taenia solium cysticerci cDNA library; it contains at least a B-cell epitope and a T-cell epitope capable of stimulating CD8+ and CD4+ proliferation. Additionally, it has been observed that supernatant of cells specifically stimulated with this peptide contains high IFN-γ levels, as well as IL-2 and in a lesser degree IL-4. Similar results were obtained when cytokine production was measured in T-cells by flow cytometry, which points to the peptide capacity to promote an inflammatory response [Toledo A et al. Infection Immun 1999; 67 (5): 2522-30].
GK-1 peptide is capable by itself of enhancing the activation state of cells participating in antigen presentation (macrophages and dendritic cells). When administered conjointly with vaccine antigens, GK-1 has showed to increase the vaccine-induced protective immune response, measured in terms of the amount of produced antibodies and the recovered viral titer after challenge.
On patent MX228767, M13 filamentous phage is described as having the capacity of exacerbating the specific immune response when administered subcutaneously or intranasally.
On Manoutcharian K et al. Vet Immunol Immunopathol 2004; 99: 11-24, the protective capacity against murine and porcine cysticercosis of CPhV vaccine, composed by recombinant phages KETc1, KETc12, GK1, and KETc7 (4×1012 phage particles), is described. It was shown that CPhV elicits a specific cellular immune response, but not a humoral one.
On Morales J et al. Vaccine 2008; 26: 2899-2905, the phagemid is revealed as a component of the recombinant vaccine against cysticercosis named S3Pvac-phage.
On Morales J et al. Vet Parasitol 2011; 176: 53-58, the capacity of S3Pvac-phage vaccine to reduce the prevalence of cysticercosis (caused by Taenia solium) and hydatidosis (caused by the tapeworm Echinococcus granulosus) in pigs is described. This effect is due to the cross-reactivity given the high homology of the vaccine components in both cestodes.